Previous studies have suggested that adult hippocampal neurogenesis (AHN) plays a role in cocaine memory formation. Here, we showed that Tau was significantly downregulated in the hippocampus in the cocaine memory formation. Tau knock-out (KO) promoted AHN in the hippocampal dentate gyrus (DG), resulting in the enhanced memory formation evoked by cocaine-cue stimuli. In contrast, genetically overexpressed 4R Tau in the hippocampus disrupted cocaine-cue memory by suppressing AHN. In addition, 4R Tau interacted directly with phosphoinositide 3-kinase (PI3K)-p85 and hindered its nuclear translocation, eventually repressing PI3K-AKT signaling, which is essential for hippocampal neuronal proliferation.In sensory systems of the brain, mechanisms exist to extract distinct features from stimuli to generate a variety of behavioral repertoires. These often correspond to different cell types at various stages in sensory processing. In the mammalian olfactory system, complex information processing starts in the olfactory bulb, whose output is conveyed by mitral cells (MCs) and tufted cells (TCs). Despite many differences between them, and despite the crucial position they occupy in the information hierarchy, Cre-driver lines that distinguish them do not yet exist. Here, we sought to identify genes that are differentially expressed between MCs and TCs of the mouse, with an ultimate goal to generate a cell type-specific Cre-driver line, starting from a transcriptome analysis using a large and publicly available single-cell RNA-seq dataset (Zeisel et al., 2018). Many genes were differentially expressed, but only a few showed consistent expressions in MCs and at the specificity required. After further validating theserated a transgenic mouse line that enables mitral cells to be specifically labeled or manipulated. This was achieved by looking for genes that are specific to mitral cells using a large and public gene expression dataset, and creating a transgenic mouse using the gene editing technique, CRISPR/Cas9. This will allow scientists to better investigate parallel information processing underlying the sense of smell.The map of category-selectivity in human ventral temporal cortex (VTC) provides organizational constraints to models of object recognition. One important principle is lateral-medial response biases to stimuli that are typically viewed in the center or periphery of the visual field. However, little is known about the relative temporal dynamics and location of regions that respond preferentially to stimulus classes that are centrally viewed, like the face- and word-processing networks. Here, word- and face-selective regions within VTC were mapped using intracranial recordings from 36 patients. Partially overlapping, but also anatomically dissociable patches of face- and word-selectivity were found in VTC. In addition to canonical word-selective regions along the left posterior occipitotemporal sulcus, selectivity was also located medial and anterior to face-selective regions on the fusiform gyrus at the group level and within individual male and female subjects. These regions were replicated using 7 Tesla fMRI d. However, it remains unclear how regions that process objects that are viewed centrally, like words and faces, are organized relative to one another. Here, invasive and non-invasive neuroimaging suggests there is a mosaic of regions in ventral temporal cortex that respond selectively to either words or faces. These regions display differences in the strength and timing of their responses, both within and between brain hemispheres, suggesting they play different roles in perception. These results illuminate extended, bilateral, and dynamic brain pathways that support face perception and reading.The sense of balance relies on vestibular hair cells, which detect head motions. Mammals have two types of vestibular hair cell, I and II, with unique morphological, molecular, and physiological properties. Furthermore, each hair cell type synapses on a unique form of afferent nerve terminal. Little is known about the mechanisms in mature animals that maintain the specific features of each hair cell type or its post-synaptic innervation. We found that deletion of the transcription factor Sox2 from type II hair cells in adult mice of both sexes caused many cells in utricles to acquire features unique to type I hair cells and to lose type II-specific features. This cellular transdifferentiation, which included changes in nuclear size, chromatin condensation, soma and stereocilium morphology, and marker expression, resulted in a significantly higher proportion of type I-like hair cells in all epithelial zones. Furthermore, Sox2 deletion from type II hair cells triggered non-cell autonomous changes in vestibular ntain the cell-specific features of type II hair cells and their post-synaptic terminals in adult mice. This is the first evidence of a molecule that maintains the phenotypes of hair cells and, non-cell autonomously, their post-synaptic partners in mature animals.Alzheimer disease (AD) is characterized by the extensive deposition of amyloid-β peptide (Aβ) in the brain. Brain Aβ level is regulated by a balance between Aβ production and clearance. The clearance rate of Aβ is decreased in the brains of sporadic AD patients, indicating that the dysregulation of Aβ clearance mechanisms affects the pathological process of AD. Astrocytes are among the most abundant cells in the brain and are implicated in the clearance of brain Aβ via their regulation of the blood-brain barrier, glymphatic system, and proteolytic degradation. The cellular morphology and activity of astrocytes are modulated by several molecules, including ω3 polyunsaturated fatty acids, such as docosahexaenoic acid, which is one of the most abundant lipids in the brain, via the G protein-coupled receptor GPR120/FFAR4. In this study, we analyzed the role of GPR120 signaling in the Aβ-degrading activity of astrocytes. Treatment with the selective antagonist upregulated the matrix metalloproteinase (MMP) inhibite and obesity in peripheral organs. https://www.selleckchem.com/products/azd4547.html However, the pathophysiological role of GPR120 in Alzheimer disease remains unknown. We found that selective inhibition of GPR120 signaling in astrocytes increased the Aβ-degrading activity of matrix metalloproteases. Our results suggest that GPR120 in astrocytes is a novel therapeutic target for the development of anti-Aβ therapeutics.